Coronary Flow Reserve In Patients Research Articles

Impaired coronary flow reserve in patients with poor type 2 diabetes control: Preliminary results from prospective microvascular dysfunction registry.

Type 2 diabetes (DM) is a common comorbidity associated with cardiovascular disease, especially when poor glucose control is present. Extracardiac microcirculatory complications prevalence is well documented, however coronary microcirculatory dysfunction (CMD) seem to be underreported in this group. The present study analyzed coronary physiology measurements (coronary flow reserve [CFR], index of microcirculatory resistance [IMR], resistance reserve ratio [RRR]) in 47 diabetic patients (21 subjects with poor glycemia control defined as fasting glucose levels > 7.2 mmol/L and 26 with normal fasting glucose), and compared to 54 non-diabetic controls, who had undergone coronary angiography due to symptoms of chronic coronary syndrome. The median age of patients was 65.5 [59.0; 73.0] years old, 74% male, similar in terms of cardiovascular risk factors and prior myocardial infarction. Insulin was used by 19% of diabetic patients with poor glucose control and by 15% of those with DM and low fasting glucose. Prevalence of CMD was 38% in poor glycemia control patients, 27% in DM-patients with proper glucose control and 31% of non-diabetics. Median CFR values were the lowest in poor DM control patients compared to both, normal fasting glucose (1.75 [1.37; 2.32] vs. 2.30 [1.75; 2.85], p = 0.026) and to non-diabetics (1.75 [1.37; 2.32] vs. 2.15 [1.50; 2.95], p = 0.045). Levels of IMR, RRR and MRR did not differ significantly between compared groups (p > 0.05 for all comparisons). Poor glycemia control in type 2 DM might be associated with a higher prevalence of CMD driven by decreased coronary flow reserve, however, further research in larger groups of patients should be performed to confirm this observation.

Relationship between peri-coronary inflammation and coronary vascular function in patients with suspected coronary artery disease.

In this study, we aim to investigate the relationship between the attenuation of peri-coronary adipose tissue (PCAT) in patients with suspected coronary artery disease (CAD) and the assessment of coronary vascular functions using coronary flow reserve (CFR). We included 364 patients who underwent 13N-NH3 positron emission tomography/computed tomography and coronary computed tomography angiography (CCTA). We determined the relationship between fat attenuation index (FAI), PCAT volume, and other qualitative CT-derived anatomic parameters with CFR. We detected a decrease in CFR (<2.5) in 206 (57%) patients. At the patient level, those with reduced CFR showed a significantly higher prevalence of diffused atherosclerosis (41% vs. 23%; P < 0.001) and higher FAI (-75.5 HU vs. -77.1 HU; P = 0.014). In patients without obstructive CAD, FAI was significantly higher in those with reduced CFR (-75.5 HU vs. -77.7 HU, P = 0.026). On the vessel level, 1,092 vessels were analyzed, and 642 (59%) exhibited reduced CFR. The vessels with reduced CFR presented a significantly higher prevalence of obstructive CAD (37% vs. 26%; P < 0.001), diffused atherosclerosis (22% vs. 11%; P < 0.001), low-attenuation plaque (6% vs. 3%; P = 0.030), and positive remodeling (7% vs. 2%; P = 0.001). FAI was higher in vessels with reduced CFR (-80.8 HU vs. -81.8 HU; P = 0.045) than in normal CFR. In the patient-level analysis, obstructive CAD, diffused atherosclerosis, and FAI were independently linked with CFR. FAI was still associated with global CFR after adjusting for traditional risk factors (age, hypertension, diabetes, hyperlipidemia, and smoking). FAI remained independently associated with reduced CFR in patients without obstructive CAD. Coronary perivascular inflammation evaluated by CCTA was independently associated with coronary vascular function. In patients without obstructive CAD, FAI was higher in the presence of reduced CFR. Altogether, FAI can help reveal microcirculatory damage in patients who do not exhibit epicardial artery stenosis.

Efficacy of Angiotensin-Converting Enzyme Inhibitors in Coronary Microvascular Dysfunction: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Coronary microvascular dysfunction (CMD) is becoming increasingly recognized as an important contributor to the development of ischemic heart diseases. Without obstructive coronary artery disease, the physiological function of the coronary microcirculation can be altered by structural, functional, and molecular factors, leading to myocardial ischemia. CMD can significantly impact the quality of life and prognosis and imposes a huge financial burden on healthcare systems and people. This meta-analysis aims to investigate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) for treating CMD. A systematic literature review identified randomized controlled trials (RCTs) comparing ACEIs with placebo in CMD patients. Review Manager, 5.3 for Windows, was utilized. Using the Mantel-Haenszel (M-H) method, improvement in coronary flow reserve (CFR) and systolic blood pressure events was pooled as mean difference (MD) in a meta-analysis model with a fixed effect model, whereas the number of chest pain episodes was pooled as MD with a random effect model. Five randomized controlled trials involving 209 patients were included in the analysis. The analysis demonstrated a statistically significant improvement in CFR in the ACEIs group compared to the placebo group (MD -0.3, 95% CI -0.61 to 0.01, P = 0.05). However, there was no significant difference in the number of chest pain episodes between the ACEIs and placebo groups (MD 1.79, 95% CI -3.99 to 7.58, P = 0.54). Similarly, no significant difference in blood pressure change was observed between the two groups (MD 4.02, 95% CI -3.25 to 11.28, P = 0.28). In conclusion, the appropriate treatment for CMD is a source of contention because adequate data is lacking. Our findings suggest that ACEIs may have a positive effect on improving CFR in patients with microvascular angina. However, ACEIs did not demonstrate a significant impact on the number of chest pain episodes or systolic blood pressure in this patient population. Further research, including RCTs with larger sample sizes and longer follow-up durations, is warranted to provide more conclusive evidence on the role of ACEIs in CMD management.

Coronary Flow Reserve and Myocardial Resistance Reserve Changes After Transcatheter Aortic Valve Implantation in Aortic Stenosis

Aortic valve stenosis (AS) induces an alteration in hemodynamic conditions that are responsible for coronary microvasculature impairment. Relief of AS by transcatheter aortic valve implantation (TAVI) is expected to improve the coronary artery hemodynamic. We aimed to assess the midterm effects of TAVI in coronary flow reserve (CFR) and myocardial resistance reserve (MRR) by a continuous intracoronary thermodilution technique. At-rest and hyperemic coronary flow was measured by a continuous thermodilution technique in 23 patients with AS and compared with that in 17 matched controls, and repeated 6 ± 3 months after TAVI in 11 of the patients with AS. In patients with AS, absolute coronary flow at rest was significantly greater, and absolute resistance at rest was significantly less, than in controls (p <0.01 for both), causing less CFR and MRR (1.73 ± 0.4 vs 2.85 ± 1.1, p <0.01 and 1.95 ± 0.4 vs 3.22 ± 1.4, p <0.01, respectively). TAVI implantation yielded a significant 35% increase in CFR (p >0.01) and a 39% increase in MRR (p <0.01) driven by absolute coronary flow at rest reduction (p = 0.03). In patients with AS, CFR and MRR determined by continuous thermodilution are significantly impaired. At 6-month follow-up, TAVI improves these indexes and partially relieves the pathophysiologic alterations, leading to a partial restoration of CFR and MRR.

Association of microvascular dysfunction with cardiovascular outcomes in heart failure with preserved ejection fraction

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a disease that portends an increased risk of morbidity and mortality. Studies have reported an association between HFpEF and microvascular dysfunction, however this association and its prognostic significance remain unclear. The purpose of this meta-analysis is to evaluated the association of microvascular dysfunction with cardiovascular outcomes in patients with HFpEF. Methods A literature search was conducted for studies evaluating the association between microvascular dysfunction measured with global myocardial flow reserve (GMFR) and coronary flow reserve (CFR) and major adverse cardiovascular events (MACE) in patients with HFpEF. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow up duration was one year. Results A total of 5 studies with 448 patients (252 with HFpEF, 196 healthy controls) met inclusion criteria for evaluation of the association of GMPR with HFpEF. Patients with HFpEF had a significantly lower GMPR compared to healthy controls (SMD -0.83, 95% CI -1.03,-0.63; p&amp;lt;0.01). Heterogeneity was moderate: Chi2=9.5, df=4, I2 = 58%. Only 2 studies were identified that reported on the evaluation of CFR in patients with HFpEF so meta-analysis could not be reliably performed. A total of 4 studies with 591 HFpEF patients (284 with reduced CFR and 307 with normal CFR) met inclusion for evaluating the association with MACE. Mean follow-up was 36 months. Patients with impaired CFR &amp;lt;2.0 had significantly higher risk of MACE compared to patients with normal CFR (OR 8.89, 95% CI 3.77-20.92; P&amp;lt;0.01). Heterogeneity was low: Chi2=4.77, df=3, I2=37%. Conclusion Patients with HFpEF have significant microvascular disease compared to patients without HFpEF, which is associated with an increased risk of MACE. Additional high-quality studies are required to further elucidate this association and determine the utility of targeted medical therapy.

Speckle tracking echocardiography allows for the detection of subclinical myocardial dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement

Abstract Background Speckle tracking echocardiography (STE) is helpful for the detection of subclinical systolic function abnormalities. Coronary flow reserve (CFR) measured by dynamic 99mTc-MIBI SPECT-CZT gamma camera allows the diagnosis of myocardial perfusion defects in patients with suspected coronary artery disease (CAD). Purpose The aim of our study is to assess the diagnostic value of STE and SPECT-based CFR in patients with suspected coronary artery disease (CAD). Methods 85 patients (pts) (37.6% females, mean age 65.4 ± 8.5 years) with suspected CAD underwent 2D and 3D STE, as well as myocardial perfusion study with novel solid-state CZT nuclear camera (dipyridamole stress protocol). We calculated global longitudinal left ventricular strain (GLS), as well as LS of individual coronary artery territories (LAD LS, Cx LS and RCA LS). Total CFR and CFR in three coronary territories were also measured. The presence of CAD (coronary artery stenosis &amp;gt; 70%) was assessed by coronary angiography. Results Significant CAD was confirmed in 50 patients. Mean total CFR (1.71 ± 0.61 vs 2.1 ± 0.52, p = 0.002), as well as CFR in LAD territories (1.54 ± 0.68 vs 1.91 ± 0.56, p = 0.02), RCA territories (1.58 ± 0.82 vs 1.95 ± 0.68, p = 0.048) and Cx territories (1.58 ± 0.78 vs 2.08 ±0.76, p = 0.01) were lower in pts with CAD. In the ROC curve analysis of total CFR for the diagnosis of CAD the AUC was found to be 0.7 (p = 0.001). Mean absolute 2D GLS in pts with total CFR &amp;lt; 2.0 was significantly lower than in pts with CFR &amp;gt;= 2.0 (-14.5 ± 4.3 vs -16.9 ± 3.4, p = 0.005). Similar differences were observed in all three coronary territories (p ≤ 0.05). The same results were not observed in case of 3D GLS . Modest but significant correlations were detected between total CFR and 2D GLS values (r = -0.38; p &amp;lt; 0.001), LAD CFR and 2D LAD LS (r = -0.33; p = 0.002), LCx CFR and 2 D LCx LS (r = -0.39; p &amp;lt; 0.001), total CFR and EF (r = 0.36; p &amp;lt; 0.001). GLS at rest had good diagnostic value for detecting total CFR &amp;lt; 2 (AUC= 0.7; p = 0.004). The criterion with the highest diagnostic accuracy was GLS &amp;gt; (- 18.5) – its sensitivity was 84%, specificity 42%, positive predictive value 0.7, negative predictive value 0.7 and overall accuracy 66%. Conclusions CFR assessed by SPECT provides acceptable diagnostic accuracy for the detection of significant CAD. STE allows for identification of patients with subclinical dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement.

Abstract 17163: The Relationship Between TIMI Frame Count, Microvascular Resistance, and Coronary Flow Reserve in Patients With Ischemia and Nonobstructive Coronary Arteries

Introduction: Ischemia and nonobstructive coronary artery disease (INOCA) may be caused by coronary microvascular dysfunction (CMD), but coronary function testing for CMD is not routinely performed. Consensus statements include coronary flow reserve (CFR), an index of microcirculatory resistance (IMR), or coronary slow flow by corrected TIMI frame count (cTFC) &gt;25 as diagnostic for CMD. However, correlations between cTFC and invasive parameters of CMD are uncertain. Methods: Adults age ≥ 18 with INOCA (&lt;50% stenosis by invasive coronary angiography in all major epicardial coronary arteries) were prospectively enrolled. cTFC was measured from baseline angiography of the left anterior descending artery. Invasive coronary function testing using thermodilution techniques was performed to identify CMD, defined by IMR≥25 and/or CFR&lt;2.5. Relationships between cTFC and invasively derived CMD were evaluated. Results: Ninety-seven patients (mean age 60.4 ± 11 years; 80% female) underwent assessment; coronary slow flow was present in 46%. Coronary slow flow (cTFC&gt;25) had a sensitivity of 50%, a specificity of 57%, a positive predictive value of 53%, and a negative predictive value of 54% to identify CMD defined by IMR and/or CFR. cTFC weakly correlated with IMR (r=0.40, p&lt;0.001) and was not correlated with CFR (Pearson r=-0.03, p=0.73). Areas under the receiver operating characteristic curves were calculated for cTFC to identify abnormal IMR (AUC = 0.64), CFR (AUC = 0.55), CMD (AUC = 0.59), and CMD endotypes of abnormal IMR with normal CFR (AUC = 0.65), abnormal CFR with normal IMR (AUC = 0.58), abnormal IMR and CFR (AUC = 0.54). Conclusions: Coronary slow flow by angiography was not a reliable indicator of CMD defined by abnormal IMR and/or CFR. Correlations between cTFC and IMR were poor and no correlation with CFR was observed. These findings raise questions regarding the relevance of coronary slow flow at baseline to assess microvascular pathology causing INOCA.

The prognostic value of coronary flow reserve in patients with non-obstructive coronary artery disease and microvascular dysfunction: a systematic review and meta-analysis with focus on imaging modality and sex difference.

To clarify prognosis of patients with non-obstructive coronary artery disease (NOCAD) and coronary microvascular disease (CMD) assessed as low coronary flow reserve (CFR) according to imaging modalities and sex difference. Comprehensive systematic literature review and meta-analyses were conducted. Risk of death and major adverse cardiac events (MACE) were pooled and compared in patients with abnormally low versus normal CFR using cut-off limits 2.0-2.5. Random effects model used for estimation of odds ratios (OR) and hazard ratios (HR) with 95% confidence interval (CI). Nineteen eligible observational studies provided data for death and MACE, publication bias was insignificant, p = 0.62. Risk of death and MACE were significantly higher in patients with low (n = 4.612, 29%) than normal CFR (n = 11.367, 71%): using transthoracal echocardiography (TTE) (OR 4.25 (95% CI 2.94, 6.15) p < 0.001) and (OR 6.98 (95% CI 2.56, 19.01) p < 0.001), positron emission tomography (PET) (OR 2.51 (CI 95%: 1.40, 4..49) p = 0.002) and (OR 2.87 (95% CI 2.16, 3.81) p < 0.001), and invasive intracoronary assessment (OR 2.23 (95% CI 1.15, 4.34) p < 0.018), and (OR 4.61 (95% CI 2.51, 8.48) p < 0.001), respectively. Pooled adjusted HR for death and MACE were (HR 2.45(95% CI 1.37, 3.53) p < 0.001) and (HR 2.08 (95% CI 1.54, 2.63) p < 0.001) respectively. Studies comparing men and women with abnormally low CFR demonstrated similar worse prognosis in both sexes. Low CFR is associated with poorer prognosis in patients with NOCAD regardless of sex. TTE may overestimate risk of death and MACE, while PET seems to be more appropriate. Future studies are needed to consolidate the current evidence.

Particularities of coronary physiology in patients with atrial fibrillation: insights from combined pressure and flow indices measurements.

Symptoms suggestive of myocardial ischemia are frequently encountered in patients with atrial fibrillation (AF) even in the absence of obstructive coronary artery disease. Nevertheless, an in-depth characterisation of coronary physiology in patients with AF is currently lacking. We aim to provide an insight into the characteristics of coronary physiology in AF, by performing simultaneous invasive measurements of coronary flow- and pressure- indices in a real-life population of patients with AF and indication of coronary angiography. This is a prospective open label study including patients with permanent or persistent AF and indication of coronary angiography showing intermediate coronary stenosis requiring routine physiological assessment (n = 18 vessels from 14 patients). We measured FFR (fractional flow reserve), and Doppler-derived coronary flow indices, including CFR (coronary flow reserve) and HMR (hyperaemic microvascular resistance). From the analysed vessels, 18/18 vessels (100%) presented a pathological CFR (<2.5), indicative of coronary microvascular dysfunction (CMD), and 3/18 (17%) demonstrated obstructive epicardial coronary disease (FFR ≤ 0.8). A large proportion of vessels (15/18; 83%) showed discordant FFR/CFR with preserved FFR and low CFR. 47% of the coronary arteries in patients with AF and non-obstructive epicardial coronary disease presented structural CMD (HMR ≥ 2.5 mmHg/cm/s), and were associated with high BMR and an impaired response to adenosine. Conversely, vessels from patients with AF and non-obstructive epicardial coronary disease with functional CMD (HMR < 2.5 mmHg/cm/s) showed higher bAPV. The permanent AF subpopulation presented increased values of HMR and BMR compared to persistent AF, while structural CMD was more often associated with persistent symptoms at 3 months, taking into account the limited sample size of our study. Our findings highlight a systematically impaired CFR in patients with AF even in the absence of obstructive epicardial coronary disease, indicative of CMD. In addition, patients with AF presented more prevalent structural CMD (HMR ≥ 2.5 mmHg/cm/s), characterized by reduced hyperaemic responses to adenosine, possibly interfering with the FFR assessment.

Relationship of OCT-defined plaque characteristics with CCTA-derived coronary inflammation and CMR-derived global coronary flow reserve in patients with acute coronary syndrome.

The relationship of layered plaque detected by optical coherence tomography (OCT) with coronary inflammation and coronary flow reserve (CFR) remains elusive. We aimed to investigate the association of OCT-defined layered plaque with pericoronary adipose tissue (PCAT) inflammation assessed by coronary computed tomography angiography (CCTA) and global (G)-CFR assessed by cardiac magnetic resonance imaging (CMR) in patients with acute coronary syndrome (ACS). We retrospectively investigated 88 patients with first ACS who underwent preprocedural CCTA, OCT imaging of the culprit lesion prior to primary/urgent percutaneous coronary intervention (PCI), and postprocedural CMR. All patients were divided into two groups according to the presence and absence of OCT-defined layered plaque at the culprit lesion. Coronary inflammation was assessed by the mean value of PCAT attenuation (-190 to -30 HU) of the three major coronary vessels. G-CFR was obtained by quantifying absolute coronary sinus flow at rest and during maximum hyperemia. CCTA and CMR findings were compared between the groups. In a total of 88 patients, layered plaque was detected in 51 patients (58.0%). The patients with layered plaque had higher three-vessel-PCAT attenuation value (-68.58 ± 6.41 vs. -71.60 ± 5.21 HU, P = 0.021) and culprit vessel-PCAT attenuation value (-67.69 ± 7.76 vs. -72.07 ± 6.57 HU, P = 0.007) than those with non-layered plaque. The patients with layered plaque had lower G-CFR value (median, 2.26 [interquartile range, 1.78, 2.89] vs. 3.06 [2.41, 3.90], P = 0.003) than those with non-layered plaque. The presence of OCT-defined layered plaque at the culprit lesion was associated with high PCAT attenuation and low G-CFR after primary/urgent PCI in patients with ACS. OCT assessment of culprit plaque morphology and detection of layered plaque may help identify increased pericoronary inflammation and impaired CFR, potentially providing the risk stratification in patients with ACS and residual microvascular dysfunction after PCI.

Resting coronary flow drives the daily pattern in coronary flow reserve in patients with chest pain without obstructive epicardial stenosis.

Ischemia with no obstructive coronary artery disease (INOCA) is a risk factor for major adverse cardiovascular events and is characterized by abnormal coronary microvascular tone. In patients with INOCA, adverse cardiovascular events most commonly occur in the morning compared to other times of the day and night. We tested whether coronary microvascular function varies diurnally with attenuation in the morning in patients with symptomatic coronary artery disease without significant (>50%) epicardial stenosis. We evaluated data from 17 patients studied in the AM (700-1159 h) and 11 patients in the PM (1200-1800 h). Coronary microvascular function was measured using perfusion contrast imaging at rest and after infusion of intravenous regadenoson. We calculated microvascular flow reserve as the ratio of hyperemic to resting flow. Along with independent sample t-tests, we performed bootstrapping procedures to test mean differences between AM and PM groups, using the bias-corrected and accelerated method with 5,000 bootstrapped samples. The AM and PM groups were matched for demographic and existing risk factors. Coronary microvascular flow reserve was ∼33% higher in the AM compared to the PM (P = 0.025, BCa 95% CI [0.25, 1.64]; Hedge's g = 0.89, 95% CI [0.11, 1.66]) as a result of significantly lower resting flow (∼50%) in the AM compared to the PM (P = 0.03, M Diff = -56.65, BCa 95% CI [-118.59, -2.12]; Hedge's g = -0.86, 95% CI [-1.60, -0.06]). Our observations are of clinical value and can influence diagnosis and treatment in the clinic based on the time of day of measurements.

26 CORONARY MICROVASCULAR DYSFUNCTION: IT COULD BE (ALSO) A MAN'S WORLD!

Abstract Introduction Coronary microvascular dysfunction (CMD) is one of the possible manifestation of ischaemic heart disease with signs and symptoms of myocardial ischaemia, but no obstructive coronary artery disease (CAD). CMD is defined by an impaired coronary flow reserve owing to functional and/or structural abnormalities of the microcirculation and it is associated with adverse cardiovascular prognosis. Women are known to be more likely than men to have angina in the absence of obstructive CAD and CMD has been proposed as one of the major reasons for this presentation. However, also in men, CMD should be recognized, in order to give the best treatment to relieve symptoms and improve patient prognosis. Index of microvascular resistance (IMR) and coronary flow reserve (CFR) are needed to diagnose CMD and are now easily obtained with pressure wires measurement. Methods Since the adoption in our Cath Lab of the PressureWire™ X Guidewire with the Coroventis CoroFlow Cardiovascular System (Abbott) we started to study IMR and CFR in patients with no obstructive CAD and typical angina. No acute coronary syndromes have been studied in our Cath Lab so far. In this brief study we report a descriptive analysis of the first patients studied and of the first period of follow-up, focusing on men. Results From January 2022 (date when we received the new software) to April 2022 we studied 24 patients and 8 (33%) were men. Among men, mean age was 58±5 yo and two have been already treated with PCI during the previous 6 months. Mean ejection fraction was 57±2% and mean GFR was 76±20 ml/min/mq. 7 out of 8 patients were affected by dyslipidemia, 5 were smoker, 50% were affected by arterial hypertension and only 1 by diabetes. Mean RFR and FFR in left anterior descending artery were 0.92±0.02 and 0.92±0.03, respectively. In 6/8 (75%) patients IMR derived was &amp;gt;25 and, among them 4 (66%) had CFR&amp;lt;2. After coronary study we tried to optimize medical therapy in all these patients, adding or changing to Zofenopril previous ACE inhibitor therapy, adding or titrating Ranolazine and adding or titrating negative chronotropic therapy (beta blockers or calcium channel blockers). After therapy optimization none of the patients had resumption of symptoms (follow-up from 3 to 7 months). Conclusions Even if historically considered a women's disease, we should remember that CMD also affects men. New widespread technologies should be used systematically to rule out CMD and to define patients’ symptoms mechanisms. This would lead to targeted therapy that could improve patient's lives.

Prognostic Impact of Coronary Flow Reserve in Patients With CKD

Both coronary flow reserve (CFR) and chronic kidney disease (CKD) are known to be associated with adverse cardiac events. However, it is unclear how these prognostic factors are interrelated. This study evaluated the association between intracoronary physiologic indexes and CKD and their prognostic implications. A total of 351 patients without left ventricular systolic dysfunction (ejection fraction≥ 40%) and not on dialysis whose revascularization was deferred based on fractional flow reserve (FFR) > 0.80 were analyzed. Depressed CFR was defined as CFR≤ 2.0. The primary outcome was a composite of cardiac death or hospitalization for heart failure at 3 years. Patients with CKD showed lower CFR than the non-CKD population (3.28 ± 1.77 vs. 2.60 ± 1.09, P< 0.001), mainly driven by increased resting coronary flow. There was no significant difference in hyperemic coronary flow, FFR, and index of microvascular resistance between the 2 groups. CFR was significantly associated with estimated glomerular filtration rate (eGFR) (P= 0.045), and the proportion of depressed CFR was significantly increased with higher CKD stages (P= 0.011). The risk of cardiac death or hospitalization for heart failure was the lowest in the non-CKD and preserved CFR group (11.9%) and the highest in the CKD and depressed CFR group (60.0%, overall log rank P< 0.001). Both CKD (adjusted hazard ratio [HRadj] 2.614, 95% confidence interval [CI] 1.505-4.539, P< 0.001) and depressed CFR (HRadj 3.237, 95% CI 2.015-5.199, P< 0.001) were independently associated with the risk of the primary outcome. There was a significant association between severity of CKD and CFR. Both CKD and depressed CFR showed independent association with higher risk of cardiac death or hospitalization for heart failure.

Additive negative prognostic value of coronary flow reserve in patients with left bundle branch block without inducible ischemia and without known coronary artery disease

Abstract Background Left bundle branch block (LBBB) can be isolated thing, but it is also often associated with underlying coronary artery disease (CAD). Stress echocardiography (SECHO) is widely used as an imaging method for the diagnosis of CAD. However, the diagnostic value of stress echocardiography in patients (pts) with LBBB is limited. Purpose To evaluate negative prognostic value of coronary flow reserve (CFR) in pts with LBBB without inducible ischemia and without known CAD. Methods This retrospective study included 224 pts (98, 43.8% male gender, average age 66±11 years) with LBBB and without known CAD. All the pts had negative SECHO test according the Bruce protocol. Risk factors for CAD (diabetes, smoking, hypertension, high cholesterol and positive family history of CAD), Duke treadmill score, functional capacity (Metabolic Equivalents - METs) were recorded in all pts. Out of 224 pts, in 64 (29.5%) coronary flow reserve on the left anterior descending artery was assessed using pulsed Doppler echocardiography with adenosine in a dose of 140μcg/kg/body weight during 3 minutes. As the normal value we took value of CFR ≥2. Median follow up of the pts was 72 months (IQR 56.25–132 months) for the occurrence of MACE (cardiovascular death (CVD), non-fatal myocardial infarction (nfMI), coronary artery bypass graft (CABG) and percutaneous coronary revascularization (PCI). Results Out of 224 pts, 6 (2.7%) had positive SECHO test, 2 pts (0.9%) had died due to non-cardiac causes and 11 pts (4.9%) were lost to follow up so they were excluded from further analysis. The remaining 204 pts were divided in 2 groups: 1. pts with only negative SECHO (n=144, 68.8%); 2. pts with negative SECHO and normal CFR (n=64, 31.2%). During the follow-up period 22 out of 205 pts (10.7%) had an adverse event (6 CVD, 6 nfMI, 5 CABG, 8 PCI). Between the two groups there was no significant difference in risk factors and parameters of the SECHO test. Pts with CFR had significantly lower rate of MACE compared to the pts with only SECHO test (2, 3.1% vs 20, 14.2%, p=0.018, respectively). Using the Cox regression analysis, univariate predictors of MACE were insulin dependent diabetes (HR 10.851 [95% CI 2.095–56.220], p=0.004), Duke score (HR 0.603 [95% CI 0.414–0.878], p=0.008), and MET (HR 0.393 [95% CI 0.209–0.737], p=0.004). In the multivariate analysis only the insulin dependent diabetes remained an independent predictor of MACE (HR 6.906 [95% CI 1.100–43.363], p=0.039). Using the Kaplan-Meier survival curve we see that the pts with SECHO test and CFR had shorter event-free time compared to the pts with SECHO test (136.3±3.6 months vs 149.8±2.9 months, Log Rank 4.022, p=0.045) (Figure 1). Conclusion Normal value of CFR has good negative prognostic value in pts with LBBB without inducible ischemia and without known CAD, while pts with insulin dependent diabetes have more pronounced risk for the occurrence of adverse events. Funding Acknowledgement Type of funding sources: None.

Relationship between OCT-derived plaque characteristics, CTA-derived coronary inflammation, and CMR-derived global coronary flow reserve in patients with acute coronary syndrome

Abstract Background The presence of layered plaque is suggestive of recurrent thrombotic events. However, the impact of layered plaque detected by optical coherence tomography (OCT) on coronary inflammation and coronary flow reserve remains unclear. Purpose We aimed to investigate the association of OCT-derived layered plaque with pericoronary adipose tissue inflammation assessed by coronary computed tomography angiography (cCTA) and global coronary flow reserve (G-CFR) assessed by cardiac magnetic resonance imaging (CMR) in patients with acute coronary syndrome (ACS). Methods We investigated 88 patients with first ACS who underwent preprocedural cCTA and OCT imaging of the culprit lesion, and CMR after percutaneous coronary intervention (PCI). All patients were divided into four groups according to the OCT-derived culprit plaque characteristics: layered vs. non-layered plaque; and plaque rupture vs. plaque erosion. Coronary inflammation was assessed by the mean value of pericoronary adipose tissue (PCAT) attenuation (−190 to −30 HU) of the three major coronary vessels. G-CFR was obtained by quantifying absolute coronary sinus flow at rest and during maximum hyperemia. CCTA and CMR findings were compared between the groups. Results In a total of 88 patients, layered plaque [L] with plaque rupture [PR] was observed in 25 patients, layered plaque with plaque erosion [PE] was observed in 26 patients, non-layered plaque [NL] with PR was observed in 23 patients, and non-layered plaque with PE was observed in 14 patients, respectively. Three-vessel-PCAT attenuation value (L-PR vs. L-PE vs. NL-PR vs. NL-PE; −68.13±6.18 vs. −69.01±6.72 vs. −69.76±4.04 vs. −74.61±5.63 HU, P=0.009) and culprit vessel PCAT attenuation value (L-PR vs. L-PE vs. NL-PR vs. NL-PE; −66.39±7.38 vs. −68.94±8.06 vs. −70.01±5.76 vs. −75.45±6.60 HU, P=0.003) showed the graded difference between the four groups. G-CFR value also showed the graded difference between the four groups (L-PR vs. L-PE vs. NL-PR vs. NL-PE; 2.26 [1.80–2.87] vs. 2.24 [1.72–3.13] vs. 2.97 [2.24–3.83] vs. 3.18 [2.67–4.08], P=0.022). Conclusions The presence of layered plaque at the culprit lesion was associated with high PCATA and low G-CFR in patients with ACS. Detection of layered plaque may indicate increased pericoronary inflammation and impaired coronary flow reserve, potentially providing the risk stratification in patients with ACS. Funding Acknowledgement Type of funding sources: None.

Hidden Coronary Atherosclerosis Assessment but Not Coronary Flow Reserve Helps to Explain the Slow Coronary Flow Phenomenon in Patients with Angiographically Normal Coronary Arteries.

The significance of the slow coronary flow phenomenon (SCFph), as visualized in patients (pts) with angiographically normal coronary arteries, is controversial. Absolute coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD), non-invasively assessed by a transthoracic color-guided pulsed-wave Doppler (E-Doppler TTE), is a reliable parameter to assess coronary microcirculatory dysfunction (CMD). Mild and angiographically hidden epicardial atherosclerosis (Hath), as visualized by intracoronary ultrasound (IVUS), which could be the clue to atherosclerotic coronary microvascular involvement, has never been investigated together with CFR in patients. This study was aimed at assessing the value of CFR and HA in explaining the SCFph. Methods. Both non-invasive assessment of CFR in the LAD and corrected TIMI frame count assessment of the coronary contrast runoff were performed in 124 pts with angiographically normal coronary arteries. Among the whole group, 32 patients also underwent intracoronary ultrasounds in the LMCA and LAD, and the maximal plaque burden was assessed (Lesion external elastic (EEM) cross sectional area (CSA)—Lesion Lumen CSA/Lesion EEM CSA * 100). We found that 24 of the 124 pts (group 1) had the SCFph and the remaining 100 had a normal runoff (group 2). CFR, evaluated in both groups, was not significantly different, being 2.79 ± 0.79 (Mean ± SD) in group 1 and 2.90 ± 0.8 in group 2 (p = ns); in the pts also examined by IVUS (32 pts), the SCFph was always associated with hidden atherosclerosis, and a plaque burden of ≥33%. On the contrary, in the normal runoff group, any grade of PB was observed (from no athero to a PB > 70%) and remarkably, 10 pts had no signs of athero or just a minimal plaque burden. This resulted in a ROC curve analysis in which PB < 33% had a high negative predictive value (100%) in ruling out the SCFph. In addition, considering a CFR value < 2.21 as an index of coronary microcirculatory dysfunction, we found CMD in 15 pts (15%) in group 1 and in 7 pts (29%) in group 2 (p = ns). In conclusion, the SCFph is strongly connected to epicardial athero to the extent that the absence of hidden coronary athero has a very high negative predictive power in ruling out SCFph. CFR that is based on an endothelium-independent mechanism remains fairly normal in this condition. An endothelium-dependent microcirculatory constriction at rest due to atherosclerotic involvement of the coronary microvascular network is a possible explanation of the SCFph.

Prognostic Impact of Coronary Flow Reserve in Patients With Reduced Left Ventricular Ejection Fraction.

BackgroundIntracoronary physiologic indexes such as coronary flow reserve (CFR) and left ventricular ejection fraction (LVEF) have been regarded as prognostic indicators in patients with coronary artery disease. The current study evaluated the association between intracoronary physiologic indexes and LVEF and their differential prognostic implications in patients with coronary artery disease.Methods and ResultsA total of 1889 patients with 2492 vessels with available CFR and LVEF were selected from an international multicenter prospective registry. Baseline physiologic indexes were measured by thermodilution or Doppler methods and LVEF was recorded at the index procedure. The primary outcome was target vessel failure, which was a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization over 5 years of follow‐up. Patients with reduced LVEF <50% (162 patients [8.6%], 202 vessels [8.1%]) showed a similar degree of epicardial coronary artery disease but lower CFR values than those with preserved LVEF (2.4±1.2 versus 2.7±1.2, P<0.001), mainly driven by the increased resting coronary flow. Conversely, hyperemic coronary flow, fractional flow reserve, and the degree of microvascular dysfunction were similar between the 2 groups. Reduced CFR (≤2.0) was seen in 613 patients (32.5%) with 771 vessels (30.9%). Reduced CFR was an independent predictor for target vessel failure (hazard ratio, 2.081 [95% CI, 1.385–3.126], P<0.001), regardless of LVEF.ConclusionsCFR was lower in patients with reduced LVEF because of increased resting coronary flow. Patients with reduced CFR showed a significantly higher risk of target vessel failure than did those with preserved CFR, regardless of LVEF.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.

Low coronary flow reserve in patients with long-standing persistent atrial fibrillation is associated with worse clinical outcomes

Abstract Funding Acknowledgements Type of funding sources: None. Background / Introduction Atrial fibrillation (AF) is associated with an increased risk of myocardial infarction, stroke and all-cause mortality. Myocardial perfusion imaging (MPI) is well-established for the diagnosis of coronary artery disease (CAD) and risk-stratification in sinus rhythm (SR) patients. Purpose The aim of this study was to determine the prognostic impact of AF and coronary flow reserve (CFR) in patients undergoing positron emission tomography (PET) MPI. Methods 680 patients without a known history of CAD were included. 226 paroxysmal AF (PAF) and 114 long-standing persistent AF (LSPAF) patients were identified from a prospective PET MPI registry in the Isala Hospital and propensity matched in a 1:1 ratio to SR patients. The main indications for PET MPI were chest pain and dyspnea. Follow-up was obtained for the occurrence of major adverse cardiac and cerebrovascular events (MACCE, composite of myocardial infarction (MI), stroke/transient ischemic attack (TIA) or all-cause death). Results Compared with patients with PAF, patients with LSPAF were older (p=0.011) and more frequently male (p=0.031), with no significant differences in medical history. There were no significant differences between SR and AF in the occurrence of MACCE during a mean follow-up of 36 months. However, the incidence of downstream coronary angiography (p&amp;lt;0.001) and MACCE (p=0.028) was higher in patients with LSPAF compared to those with PAF and SR. A low CFR (defined as CFR below the median of 2.4) in patients with LSPAF showed significantly more MACCE compared with SR and PAF (p&amp;lt;0.001). Moreover, LSPAF was an independent predictor of MACCE (odds ratio 1.667, 95% confidence interval 1.028±2.705). Conclusion Low CFR in patients with LSPAF is associated with a higher incidence of MI, stroke/TIA and death compared with low and normal coronary flow parameters in patients with SR and PAF.

Differential Prognostic Value of Revascularization for Coronary Stenosis With Intermediate FFR by Coronary FlowReserve.

The authors sought to evaluate comparative prognosis between deferred versus performed percutaneous coronary intervention (PCI) according to coronary flow reserve (CFR) values of patients with intermediate fractional flow reserve (FFR). For coronary stenosis with intermediate FFR, the prognostic value of PCI remains controversial. The prognostic impact of PCI may be different according to CFR in patients with intermediate FFR. From the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry, N=2,322), 400 patients (412 vessels) with intermediate FFR (0.75-0.80) were selected. Patients were stratified into preserved CFR (>2.0, n=253) and depressed CFR (≤2.0, n=147) cohorts. Per-vessel clinical outcomes during 5 years of follow-up were compared between deferred versus performed PCI groups in both cohorts. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. Among the study population, PCI was deferred for 210 patients (219 vessels, 53.2%) (deferred group) and performed for 190 patients (193 vessels, 46.8%) (performed group). The risk of TVF was comparable between the deferred and performed groups (12.8% vs 14.2%; adjusted HR: 1.403; 95%CI: 0.584-3.369; P=0.448). When stratified by CFR, PCI was performed in 39.1% (100/261 vessels) of the preserved CFR cohort and 61.9% (93/151 vessels) of the depressed CFR cohort. Within the preserved CFR cohort, the risk of TVF did not differ significantly between the deferred and performed groups (11.0% vs 13.9%; adjusted HR: 0.770; 95%CI: 0.262-2.266; P=0.635). However, in the depressed CFR cohort, the deferred group had a significantly higher risk of TVF than the performed group (17.2% vs 14.2%; adjusted HR: 4.932; 95%CI: 1.312-18.53; P=0.018). A significant interaction was observed between CFR and the treatment decision (interaction P =0.049). Results were consistent after inverse probability weighting adjustment. In patients with intermediate FFR of 0.75 to 0.80, the prognostic value of PCI differed according to CFR, with a significant interaction. PCI was associated with a lower risk of TVF compared with the deferral strategy when CFR was depressed (≤2.0), but there was no difference when CFR was preserved (>2.0). CFR could be used as an additional risk stratification tool to determine treatment strategies in patients with intermediate FFR. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234).

Coronary flow reserve in patients with heart failure with preserved ejection fraction

Aim. To study the parameters of myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients with heart failure (HF) with preserved ejection fraction and evaluate their relationship with the severity of HF.Material and methods. The study included 47 patients (men, 68,7%) aged 65,0 (58,0; 72,0) years with left ventricular ejection fraction of 62 (56; 67)% and coronary artery stenosis &lt;50%. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by enzyme immunoassay. MBF and CFR values were assessed using cardiac single photon emission computed tomography.Results. Depending on NT-proBNP levels, the patients were divided into 2 groups (p&lt;0,001): the 1st group included (n=15) patients with NT-proBNP &lt;125 pg/ml (58,2 [41,6; 70,7] pg/ml), while in the 2nd group (n=32) — with NT-proBNP ≥125 pg/ml (511,4 [249,8; 1578,1] pg/ml). The group of patients with high NTproBNP levels was characterized by higher values (by 33,8%, p=0,0001) of resting MBF and reduced CFR (by 14,7%, p=0,001) compared with patients with normal NT-proBNP level: resting MBF — 0,65 (0,44; 0,79) vs 0,43 (0,30; 0,58) ml/min/g; CFR — 2,21 (1,52; 2,83) vs 2,59 (2,47; 3,05), respectively. At the same time, MBF at stress did not differ between the groups. The relationship of NTproBNP levels with global CFR (p=0,012; r=-0,339) and MBF at rest (p=0,012; r=0,322) was established. A stepwise decrease in global CFR was revealed depending on the NYHA class as follows (p&lt;0,001): 2,79 (2,52; 2,93); 1,8 (1,55; 2,08); 1,31 (1,23; 1,49) — for class I, II, and III, respectively.Conclusion. A decrease in CFR in patients with HF with preserved ejection fraction indicates impaired myocardial blood supply, which, in this group of patients, is associated with microcirculatory changes. At the same time, the severity of MBF alterations is closely related to HF severity.